Open AccessInhibition of Matrix Metalloproteinase with BB-94 Protects against Caerulein-Induced Pancreatitis via Modulating Neutrophil and Macrophage Activation
Author(s) -
Zengkai Wu,
Tunike Mulatibieke,
Mengya Niu,
Bin Li,
Jing Dai,
Xin Ye,
Yan He,
Congying Chen,
Li Wen,
Guoyong Hu
Publication year - 2020
Publication title -
gastroenterology research and practice
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 45
eISSN - 1687-630X
pISSN - 1687-6121
DOI - 10.1155/2020/8903610
Subject(s) - proinflammatory cytokine , medicine , acute pancreatitis , chemokine , pancreatitis , reactive oxygen species , inflammation , endocrinology , chemistry , biochemistry
Methods AP was induced in Balb/C mice by ten hourly intraperitoneal injections of caerulein (100 μ g/kg) and LPS (5 mg/kg). The MMP inhibitor, BB-94 (20 mg/kg) was intraperitoneally administered 30 min before AP induction. Pancreatitis was confirmed by histology and serum amylase and lipase. Expression of pancreatic proinflammatory mediators and NF- κ B activation were assessed. Bone marrow-derived neutrophils (BMDNs) and macrophages (BMDMs) were isolated. BMDNs were activated by phorbol 12-myristate 13-acetate (PMA, 50 ng/ml) and neutrophil reactive oxygen species (ROS) production was recorded. BMDMs were stimulated with 10 ng/ml IFN- γ and 100 ng/ml LPS to induce M1 macrophage polarization.Results Pancreatic MMP-9 was markedly upregulated and serum MMP-9 was increased in caerulein-induced pancreatitis. Inhibition of MMP with BB-94 ameliorated pancreatic tissue damage and decreased the expression of proinflammatory cytokines (TNF α and IL-6) or chemokines (CCL2 and CXCL2) and NF- κ B activation. Furthermore, using isolated BMDNs and BMDMs, we found that inhibition of MMP with BB-94 markedly decreased neutrophil ROS production, inhibited inflammatory macrophage polarization and NF- κ B activation.Conclusions Our results showed that inhibition of MMP with BB-94 protected against pancreatic inflammatory responses in caerulein-induced pancreatitis via modulating neutrophil and macrophage activation.